HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic viral disease of the central nervous system (CNS) characterized by profound immunodysregulation and by a remarkably high frequency of virally reactive CD8+ T cells in the blood and spinal fluid. Based on the expression of surface molecules on CD8 T cells and on their relative telomeric length, it appears that CD11b+CD28- T cells and CD11b-/CD28+ T cells may define reciprocal subsets of CD8+ T cells. CD28 appears to identify a naive population of CD8+ T cells which have telomere lengths equivalent to CD4+ T cells from the same individual and can be stimulated to differentiate into cytotoxic or other effector cells by appropriate costimulation through the TCR/CD3 complex and CD28. CD28-/CD11b+ T cells, on the other hand, appear to represent an oligoclonally expanded memory phenotype, which may contain virally specific CD8+T cells, and which display shortened telomeres in comparison to their CD28+ counterparts in the same individual, thus implying many more rounds of division in the course of their oligoclonal expansion. However, the investigation of these subsets has been hampered by the difficulty in generating T cell clones. We have established conditions to routinely generate CD8+ T cell clones of both functional subsets, which allows us for the first time to investigate the functional differences between these subsets at the biochemical level. We have demonstrated differences in T cell activation and cytokine secretion between the subsets in normal individuals, both in freshly isolated PBMC and at the clonal level. We hypothesize that CD8+/CD11b+ T cells represent a preactivated and virally specific population in vivo. Investigation of this subset at the molecular level will provide important information regarding human CD8+ T cell biology, both in HAM/TSP as well as in other chronic viral infections, such as HIV disease, and in normal immune responses.